1,2,4-4h-triazole derivatives

ABSTRACT

SUBSTITUTED 1,2,4-4H-TRIAZOLES OF THE FORMULA   3-R1,4-R2,5-R3-4H-1,2,4-TRIAZOLE   OR A TAUTOMERIC FORM THEREOF, ARE FUNGICIDES PARTICULARLY USEFUL FOR THE CONTROL OF RUSTS. CERTAIN OF THESE COMPOUNDS ARE SYSTENIC IN ACTION, GIVING EXCELLENT CONTROL OF CEREAL RUSTS, NOTABLY WHEAT RUST, AND ARE PARTICULARLY EFFECTIVE AS SEED TREATMENTS.

United States Patent Offlce 3,701,784 Patented Oct. 31, 1972 US. Cl. 260-308 R 4 Claims ABSTRACT OF THE DISCLOSURE Substituted 1,2,4-4H-triazoles of the formula will in or a tautomeric form thereof, are fungicides particularly useful for the control of rusts. Certain of these compounds are systemic in action, giving excellent control of cereal rusts, notably wheat rust, and are particularly effective as seed treatments.

This application is a continuation-in-part of US. Ser. No. 757,490, filed Sept. 4, 1968. This invention is concerned with substituted 1,2,4-'4H-triazoles which possess fungicidal properties useful for the control of fungal diseases on plants and to agricultural compositions containing them. It also relates to certain of these 1,2,4-4H-triazoles which are novel compounds and to their method of preparation. Further, it relates to certain 1,2,4-4H-triazoles which are useful as systemic fungicides for the control of rust diseases, as on cereal crops.

The chemistry of the 1,2,4-triazoles has been reviewed by K. T. Potts in Chemical Reviews 61, 87-127 (1961). A few such compounds are known to possess biological properties. 3-arnino-l,2,4-triazole is a commercial herbicide, and thiocarbamyl derivatives of it possess fungicidal properties useful for paints according to French Pat. 1,425,253.. Japanese Pat. =Pub1. 11,480/ 66 disclosed certain 3-mercapto-4-amino-5-(substituted-methyl) 1,2,4-4H-triazoles as fungicides. 5 amino 1 [bis(dimethylamino)- phosphinyl]-3-phenyl-1,2,4-triazole is a known fungicide. US. Pat. 3,308,131 discloses among others 3-mercapto-l- (substituted-carbamyl) 1,2,4 triazoles useful as insecticides.

Relatively few compounds are known to control fungal rust organisms and still fewer which control them by systemic action. Rust fungicides include symmetrical-dichlorotetrafiuoroacetone, ethylenebisdithiocarbamates, nickel compounds, phenylhydrazones, cycloheximide and certain carboxamido ox-athiins.

The substituted 1,2,4-4H triazoles of this invention which have been found useful as fungicides for the control of phytopathogenic fungi are represented by the general formula wherein R is hydrogen or --SA wherein A is substituted aryloxy; aryl; alkoxy, alkyl, halo preferably chloro or nitro substituted aryl; benzoyl and halo preferably chloro, alkoxy, alkyl or nitro substituted benzoyl,

(c) the group O(X)R wherein X is O or S and R is selected from the group consisting of aryl, lower alkyl substituted aryl, lower alkoxy substituted aryl, halo and nitro substituted aryl, furoyl, and the group NR 'R wherein R and R may be hydrogen or lower alkyl groups,

(d) the group -CH C(O)NR R wherein R and R have the above meaning,

(e) the group CH(OH)R wherein R" is hydrogen,

lower alkyl or lower halo-substituted alkyl,

(f the group wherein C and D are hydrogen and a meta-directing group such as cyano, nitro, sulfonic acid and sulfonic acid derivatives with the proviso that only one of C and D may be hydrogen,

(g) salt-forming metals such as the alkali and alkaline earth metals, cadmium, copper, iron, manganese, nickel and zinc;

R is alkyl of 1-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups; cycloalkyl of 3-8 carbon atoms which may be substituted with one or more halo preferably chloro, hydroxy or nitro groups; aralkyl of up to 10 carbon atoms; aralkyl of up to 10 carbon atoms substituted in the aryl group with lower alkyl, halo preferably chloro, and nitro groups; aryl; and lower alkyl, halo prefera'bly chloro, and nitro substituted aryl; and

R is hydrogen, alkyl of 1-18 carbon atoms, hydroxy, furyl, and the group -COOB wherein B is hydrogen, alkyl of 1-1'2 carbon atoms, ammonium, ammonium monosubstituted with lower alkyl or lower hydroxyalkyl, ammonium disubstituted wit-h lower alkyl or lower hydroxyalkyl, ammonium trisubstituted with lower alkyl or lower hydroxyalkyl, quaternary ammonium and salt-forming metals; and acid salts of the basic substituted 1,2,4-4H- triazoles prepared from mineral acids such as fluo'boric, hydrobromic, hydrochloric, nitric, phosphoric and sulfuric and from mono and polybasic organic acids such as acetic, chloroacetic, acrylic, toluene-sulfonic, oxalic and maleic.

When the term lower is employed in conjunction with alkyl and alkoxy as above it is intended to indicate that the alkyl or alkyl portion thereof has a carbon content of 1 to 5 carbon atoms. Alkyl groups as referred to for Formula I may be straight or branched chain.

Compounds of Formula I in which R is SH may exist in tautomeric form; thus,

NN NNH Rn s: R" s N N l,

(II) (III) Formula II is a 1,2,4-4H-triazole whereas Formula III is more properly known as a A -1,2,4-triazoline-5-thione. Compounds derived from such a tautomeric mixture by introduction of an A group, as defined above except possibly for metallic salts, could therefore exist as or asmixtures of these. However, for the present purpose these compounds will be referred to as 1,2,4-'4H-triazoles. Further when R is OI-I two additional tautomers are possible, thus,

NN H-NN HOIL JLSA o=L J-ss N N la 1'1 It is quite probable that the major component is in the lactam form; however, for the present purpose the hydroxy-1,2,4-4H-triazole form will be used. For a general discussion of tautomeric compounds and of the isomers that may result from synthetic procedures for producing triazoles references is made to Elderfield, Heterocyclic Compounds, John Wiley, New York, 1957, vol. V, pp. 91-92.

Various methods are available for the preparation of the compounds of Formula I.

(A) For the compounds where R and R are hydrogen,

The method of Bartlett and Humphrey J. Chem. Soc. 1967, 1664-1666, involving a transamination of N,N-dimethylformamide azine may be used; thus The reaction usually involves heating to remove the dimethylamine and may be run in the presence of a solvent such as an aromatic hydrocarbon. An acidic catalyst may be used.

The method of Pellizzari (Chemical Reviews 61, 95 (1961)) involves diformhydrazide with primary amines; thus (B) For the compounds where R is SH and R is hydrogen,

it: v11

This involves reaction of hydrazine with an isothiocyanate (R NCS) to produce a semicarbazide which is then formylated followed by cyclization in the presence of a base catalyst; thus This general method is described in Organic Syntheses 40, 99 (1960) and Kroger, Sattler and Beyer Annalen 643, 128 (1961). The formation of the semi carbazide and its formylation are standard type reactions, e.g. see Lieber, Pillai and Hites Canadian Journal of Chemistry 35, 832 (1957). These intermediates may, if desired, be isolated prior to the cyclization reaction. The cyclization reaction may be conveniently carried out in the presence of a base catalyst. Cyclization may be optimized by the use of from 2 to 3 equivalents of the base catalyst. The cyclization catalyst can be selected from inorganic base catalysts such as metal hydroxides, carbonates and bicarbonates, or organic base catalysts such as triethylamine, pyridine and N,N-dimethyl-aniline. Sodium hydroxide is a readily available base catalyst for use in the cyclization reaction.

VII

Since the intermediate products, prior to cyclization are usually solids, a reaction solvent is usually necessary. The cyclization reaction may be conveniently carried out in any solvent medium that is inert under the reaction conditions. Suitable solvents are water, alcohols such as methanol, butanol and propanol, benzene, hexane, or other suitable inert organic solvents such as dimethylformamide, ether, dimethylsulfoxide, etc.

The cyclization reaction temperature is not critical. Temperatures in the range of 10 C. to C. may be used, with temperatures in the range of 25 to 75 C. being preferred.

An alternate procedure for producing compounds of Formula VII is to react the intermediate semicarbazide with ethyl formate in the presence of an alkali alkoxide, such as sodium methoxide, and heating the mixture to produce the 1,2,4-triazole; thus N a0 OH;

heat VI HzNNHC (S)NHR2 EtO OCH R (VIII) The cyclization of a l-acyl-4-substituted thiosemicarbazide with an alkaline substance or by heat has been studied as an eflicient route to compounds of Formula VIII (Chemical Reviews 61, 99 (1961)); thus An alternate procedure involves the reaction of a 4- substituted thiosemicarbazide with an acid ester, e.g. the ethyl ester, in the presence of a sodium alkoxide, e.g. sodium ethoxide; thus CzHsONa 11 0 CzHsOH VIII When in the above reaction the acid ester is a carbonate, such as ethyl carbonate, the resulting compound contains an OH group as the R substituent,

R (IX) (D) For the compounds where R is SH and R is COOH,

H O O ClNLSH This method involves reaction of a dialkyl oxalate such as diethyl oxalate with hydrazine to produce an alkyloxalyl hydrazide, which is then reacted with an isothiocyanate (R NCS) to produce a semicarbazide, followed by cyclization in the presence of a base catalyst such as sodium alkoxide or triethylamine. This produces the carboxylic ester of the Formula X compound, which upon acid hydrolysis gives the free acid. This may be illustrated with diethyl oxalate, thus EtOOC-COOEt HzNNH EIZOOCC(O)NHNH2 l-i- R NCS EtCC(O)NHNHC( S)NHR- l base catalyst 11+ 1 l X EtOOClN SH In this reaction it has been found that the formation of the alkyloxalyl hydrazide intermediate is enhanced by conducting the reaction at reduced temperatures, e.g. -10 C. to 10 C. Further, reaction and storage temperature conditions are more important with regard to the stability of the 1,2,4-triazoles having a carboxy group in the -position, i.e. when R is COOH. These compounds are readily decarboxylated when held at 130 C. for about 30 minutes or at about 45 C. for about 4 hours. An acid catalyst often produces decarboxylation under milder conditions. Thus, decarboxylation of compounds of Formula X is another way of preparing compounds of Formula VII.

(E) Compounds of the type It (XI) may be prepared by removal of the mercapto group of compounds of Formulas VIII and IX by reaction with oxidizing agents such as nitric acid or hydrogen peroxide.

(F) Salts of various of the substituted 1,2,4-triazoles may be made by methods known to one skilled in the art. Thus,

(1) the basic 1,2,4-triazoles may be reacted with mineral and organic acids, e.g. see Ainsworth et al. J. Med. Pharm. Chem. 5, 383 (1962).

(2) those compounds where R is SH group may be reacted with bases such as alkali and alkaline earth hydroxides, oxides and carbonates. Of the alkali salts the sodium salt is preferred. The relatively insoluble heavy metal salts may be made by reacting a water-soluble salt of the heavy metal with a water-soluble salt of the 1,2,4-triazole.

(3) those compounds where R is car-boxy may be reacted with metallic bases such as alkali and alkaline earth hydroxides, oxides and carbonates; ammonia and quarternary ammonium hydroxide; and amines. For some salts such as quaternary ammonium and heavy metal ones it is convenient to react a water-soluble quaternary ammonium or metal salt with a water-soluble salt of 1,2,4-triazole.

(G) Derivatives of the 1,2,4-triazoles containing a 3- mercapto group, i.e. where R in Formula I is SA, may be made by methods known to one skilled in the art. Thus,

(1) where A is alkyl; alkyl substituted with various groups such as alkoxy and aryloxy; aralkyl and substituted aralkyl; the group CH C(O)NR R and the group as defined above, the compounds may be made by reaction of the respective halides with a salt of the 3-mercapto-1,2,4-triazole.

(2) where A is an acyl group such as a benzoyl, furoyl group, carbamoyl or thiocarbamoyl, the acyl halides may be reacted with a salt of the 3-mercapto-1,2,4-triazole.

(3) where A is a lower cyanoalkyl group, the mercapto group of the 1,2,4-triazole of compounds of Formulas I, VII and VIII may be reacted with an olefinic nitrile such as acrylonitrile or methacrylonitrile. In some instances compounds of Formula V are known to result and this is particularly true for compounds which give a Michael type addition such as acrylonitrile, methacrylonitrile, acrylic acid, maleic acid, nitroethylene and nitrostyrene. A cyano group can also be introduced by other means known in the art such as replacement of a halo atom by reaction with a cyanide salt or by dehydration of a carbamoyl group.

the mercapto 1,2,4-triazoles may be reacted with an isocyanate (R NCO) or isothiocyanate (R NCS).

Details of preparing the compounds of this invention are given in the following examples which are presented for purposes of illustration and are not intended to limit the scope of the invention. Table I lists by structure and name, compounds prepared by the above-described processes and constitutes Examples 1 through 53. Table II gives physical characteristics and analyses or literature references for these examples. Specific illustrative preparations of Examples 10, 17, 22, 24, 28, 35, 36, 39, 41, 43, 48 and 49 are set forth below.

EXAMPLE 10 Preparation of 3-mercapto-4-n-butyl-1,2,4-triazole 4-n-butylthiosemicarbazide (20.0 g. or 0.136 mole) was heated to reflux with a solution of methanol (100 ml.), sodium methoxide (7.55 g. or 0.140 mole) and ethyl formate (20.7 g. or 0.280 mole). After 8 and 16 hours, 10 ml. and 5 ml. of ethyl formate was added to the refluxing solution. After 24 hours total reflux, the solvent was removed under reduced pressure and the residue was dissolved in water (100 ml.). The pH of the solution was adjusted to about 12 with 50% sodium hydroxide solution. This solution was then heated on a steam bath for 45 minutes, cooled and acidified with dilute hydrochloric acid. The resulting oil was extracted into ether. The ether was dried over sodium sulphate and removed under vacuum. The resulting oil was crystallized from ether-hexane to give 11.8 g. (55% yield) of 3-mercapto-4-n-butyl-1,2,4-triazole, MJP. 67-69 C. The structure was confirmed by its nuclear magnetic resonance spectrum and its mass spectrum.

EXAMPLE 17 Preparation of 3-mercapto-4-cyclohexyl-1,2,4-triazole Formic acid ml.) was heated on a steam bath for 15 minutes and then 4-cyclohexylthiosernicarbazide (30 g. or 0.174 mole) was added portionwise. The resulting clear solution was then heated for an additional 60 minutes, diluted with water (50 ml.) and allowed to cool at 0 C. A precipitate was formed. The precipitate (13 g. or 0.065 mole) was collected and added to a solution of sodium hydroxide (2.6 g. or 0.065 mole) in water (25 ml.) and heated on a steam bath for 60 minutes. The solution was cooled and acidified to pH 2 with dilute hydrochloric acid. The precipitate was collected and recrystallized from ethanol to give 5.3 g. of solid M.P. 162165 C. The mother liquors from the crystallization were concentrated to give an additional 4.3 g., M.P. 162-165 C. The total yield was 9.3 g. (78%) of 3-mercapto-4-cyclohexyl-1,2,4- triazole. The structure was confirmed by its nuclear magnetic resonance spectrum and its mass spectrum.

EXAMPLE 22 Preparation of 3-.mercapto-4-phenyl-S-hydroxy-1,2,4- triazole To a solution of 65 g. (0.48 mole) of phenyl isothiocyanate in 350 cc. of ether was added 50 g. (0.48 mole) of ethyl carbazate with stirring. The resulting mixture was heated on a steam bath for 0.5 hr. The precipitate was filtered off and recrystallized from ethanol2water (1:1) to give white crystals melting at 145 l46 C. Forty grams of this solid was heated with 240 cc. of 10% KOH on a steam bath for 30 min. The reaction mixture was cooled and acidified with 50% hydrochloric acid to give 25 g. of crude, air-dried solid. This was recrystallized from acetone to give 18 g. of solid melting at 135 -136 C. It is 3mercapto-4-phenyl-S-hydroxy-1,2,4-triazole, or a tautomer thereof, containing one-half molecule of water of hydration.

EXAMPLE 24 Preparation of 3-mercapto-4-methyl-5-(2-furyl)-1,2,4- triazole (A) Preparation of 1-(2-furoyl)-4-me-thyl thiosemicarbazide.Furoyl chloride (31 g. of 0.238 mole) was added dropwise to a slurry of 4-methylthiosemicarbazide (25 g. or 0.238 .mole) in dry pyridine (200 ml.) cooled to 10". The slurry was allowed to come to ambient temperature and stirred overnight. The reaction mixture was poured into 1500 ml. of crushed ice, the precipitate was collected, dried and recrystallized from EtOH to give 1- (2-furoyl)-4-methyl thiosemicarbazide (28.0 g.). This melted at 204-206 C. (dec.) and was found to contain by analysis 42.4% C, 4.6% H, 21.2% N, 16.1% 0, 15.9% S; C H N O S requires 42.2% C, 4.5% H, 21.1% N, 16.1% 0, 16.1% S. ,The structure was confirmed by its infraredspectrum and nuclear magnetic resonance spectrum.

(B) Conversion of 1-(2-furoyl)-4-methyl thiosemicarbazide into 3-mercapto-4-methyl-5-(2-furoyl)-1,2-triazole.-The above thiosemicarbazide (28 g. or 0.141 mole) in methanol (300 ml.) was refluxed overnight in the presence of sodium methoxide (15.2 g. or 0.282 mole). The solvent was then removed under vacuum and the residue was diluted with water (150 ml.). The solution was then acidified with hydrochloric acid, the precipitate was collected, washed With water and dried. The solid was recrystallized from ethanol to give 3-mercapto-4- methyl--(2-furyl)-l,2,4-triazole melting at 192194 C. The structure was confirmed by its infra-red spectrum and nuclear magnetic, resonance spectrum.

EXAMPLE 28 Preparation of 3mercapto-4-n-butyl-5carboxyl-1,2,4

triazole I (A) Preparation of l-ethyl oxalyl-4-n-butylthiosemicarbazide.To a methanolic solution (200 ml.) of diethyl oxalate (100 g. or 0.683 mole) was added a methanolic solution (200 ml.) of hydrazine hydrate (22.9 g. or 0.68 mole). The addition occurred over a two hour period during which period the reaction temperature was maintained at about 5 C. When the addition was completed n-butyl isothiocyanate (78.4 g. or 0.68 mole) was added at 5 C. The cloudy solution was stirred at ambient temperatures for 18 hours. The reaction mixture was filtered, evaporated under reduced pressures to onehalf the original volume, and diluted with water (700 ml.). The resulting precipitate was filtered and air dried to give 154.4 g. (92% yield) of l-ethyl oxalyl-4-n-butylthiosemicarbazide, M.P. 127l28 C. It was found to contain by analysis 38.76% C, 6.23% H, 19.27% N, and 14.83% S; calculated for C7H11N3O2S'H2O is 38.33% C, 5.98% H, 19.16%N and 14.63% S.

(B) Conversion of 1 ethyloxalyl 4 n-butylthiosemicarbazide into 3 mercapto-4-n-butyl-5-carboxyl-1,2,4- triazole-The thiosemicarbazide (125.0 g. or 0.507 mole) formed above was added to a solution of sodium hydroxide (45.0 g. or 1.125 moles) in water (500 ml.). After 16 hours at ambient temperature, the solution was warmed to 60 C. and cooled. Dilute (37%) hydrochloric acid (112.0 g. or 1.135 moles) was then added cautiously to avoid foaming. The resulting precipitate was filtered and dried at 45 C. in a vacuum oven to give the crude acid (96.5 g., 86% yield), M.P. 120-122" C. The acid was recrystallized from water (800 ml.) and dried to give essentially pure 3-mercapto-4-n-butyl-5-carboxy-1,2,4- triazole (67.4 g., 61% yield), M.P. 108-110" C. The structure was confirmed by its nuclear magnetic resonance spectrum and infrared spectrum.

EXAMPLE Preparation of 3methylmercapto-4-n-butyl-1,2,4- triazole Iodomethane (9.05 g. or 0.0637 mole) was added to a solution of 10 g. of 3-mercapto-4-n-butyl-1,2,4-triazole, methanol (100 ml.), and sodium hydroxide (2.55 g. or 0.0637 mole). This solution was then refluxed for 2 hours. The solvent was then removed in vacuum and the residue was dissolved in benzene. This solution was washed with water, dried and the benzene removed in vacuum. The residual oil was distilled to give 3-methylmercapto-4-nbutyl-l,2,4-triazole, B.P. 128-131 C./2 mm. The structure was confirmed by its nuclear magnetic resonance spectrum.

EXAMPLE 36 Cyanoethylation of 3-mercapto-4-n-butyl-1,2,4-triazole Acrylonitrile (12 g. or 0.224 mole) was added dropwise to a dioxane (30 ml.) solution of 3-mercapto-4-nbutyl-1,2,4-triazole (10 g. or 0.0638 mole) in the presence of a 40% aqueous solution of benzyltrimethylammonium hydroxide (1 ml.). The dark red solution was left standing overnight, and the solvent was removed in vacuum. The tarry residue was taken up in ether, washed with water, dried, and evaporated to dryness. The resulting oil was distilled to give an oil distilling at l68-175 C./2 mm. Ultraviolet spectra and the teachings of Postoviskii and Sh'egal, Chemical Abstracts 63, 13242, 1965 indicate this to be 2-(Z-cyanoethyl)4-n-butyl-1,2,4-triazoline-3- thione.

EXAMPLE 39 Preparation of 3-(1-hydroxy-2,2,2-trichloroethylmercapto)4-n-butyl-1,2,4-triazole 3-mercapto-4-n-butyl-l,2,4-triazole (2.0 g. or 0.0127 mole) and chloral (3.68 g. or 0.0254 mole) were heated in benzene (30 ml.) until a precipitate formed (10 minutes). The mixture was cooled, the precipitate was collected, dried, and recrystallized from ether-hexane to give 3-(1-hydroxy 2,2,2 trichloroethylmercapto)-4-nbutyl-l,2,4-triazole melting at "-97" C. The structure was confirmed by,its nuclear magnetic resonance spectrum.

EXAMPLE 41 Preparation of 3 (4-methoxybenzylmercapto 4-n-butyl- 1,2,4-triazole EXAMPLE 43 Preparation of 3-methylcarbamoylmercapto-4-n-butyl- 1,2,4-triazole To 6.0 g. (0.0382 mole) of 3-mercapto-4-n-butyl-1,2,4- triazole dissolved in 50 ml. of ether was added 2.5 g. (0.248 mole) of triethylamine and then 2.5 g. (0.0438

mole) of methyl isocyanate. The resulting orange-brown solution was allowed to stand overnight. The solid which formed was filtered and washed twice with 50' ml. of ether to give 4.7 g. (57% yield) of 3-methyl-carbamoylmercapt0-4-n-butyl-1,2,4-triazole melting at 1l2-114 C.

EXAMPLE 48 Preparation of 3-furoylmercapto-4-n-butyl-1,2,4-triaz01e evaporated to dryness. The solid was recrystallized from benzene to give 3-furoylmercapto-4-n-butyl-1,2,4-triazole melting at 102-105 C. The structure was confirmed by its infrared spectrum and nuclear magnetic resonance spectrum.

EXAMPLE 49 Preparation of 3-(p-methoxyphenacylmercapto)- 4-n-butyl-1,2,4-triazole To a solution of 3-mercapto-4-n-butyl-1,2,4-triazole 10 g. or 0.063 mole) and sodium hydroxide (2.55 g. or 0.0637 mole) in 200 ml. of methanol was added a-bromop-methoxyacetophenone (15.3 g. or 0.067 mole). The reaction mixture was heated at reflux for 16 hours and the solvent removed in vacuum to leave a solid residue. The solid was washed with water and recrystallized from benzene-hexane to give 3-(p-methoxy-phenacylmercapto)-4-n-butyl-1,2,4-triazole melting at 79-82 C. The structure was confirmed by its infrared and nuclear maghydroxide solution, water, dried over sodium sulfate and 20 netie spectra.

TABLE I 1, 2, 4-triazole examples Example No. R R R Name H n-C H H 4-n-propy1-1, 2, 4-triazole.

H n-CrHo H 4-n-butyl-1, 2, 4-trizaole.

H D'CBHIS H 4-n-hexyl-l, 2, 4-triazole.

H n-CioHn H 4-n-decyl-1, 2, 4-triazole.

H CH2CH2CH2O OH; H 4-(3-methoxypropyD-1, 2, 4-triazole.

H 'CHzCaH5 H 4-benzy1-1, 2, 4-trlazole.

SH CH3 H 3-mercapto-4-methy1-1, 2, 4-triazole.

SH 02H; H 3-mercapto-4-ethyl-1, 2, 4-triazole.

SH n-C H H 3-mercapt0-4-n-propyl-l, 2, 4-triaz0le.

SH t-C4H0 H 3-mercapto-44-butyl-l, 2, 4-trlazole.

SH n-O5Hu H 3-mercapto-4-n-penty1-1, 2, 4-triazole.

SH n-CaHu H 3-mercapt0-4-n-hexyl-1, 2, 4-triazole.

SH n-CaH H 3-mercapto-4-n-octyl-1, 2, 4-triazole.

SH t-OsHi-l H 3-mercapto-4-t-oetyl-1, 2, 4-trlazo1e.

SH n-CwHn H 3-mercapto4-n-deeyl-1, 2, 4-t1lazole.

SH Cyelohexyl H 3-mercapto4-cyclohexyl-1, 2, 4-tn'azole.

SH -CH2CH H 3-mercapto-4-benzyl-l, 2, 4-triazole.

SH Phenyl H 3-mereapto-4-phenyl-l, 2, 4-triaz ole.

SH CH 0H 3-rnercapto-4-methyl-5-hydroxy-1, 2,

4-trlazole.

SH 04H OH 3-mercapto-4-n-butyl-5-hydroxy-1, 2,

4-trlazole.

SH C5115 OH 3-mercapto-4-pheny1-5-hydroxy-1, 2,

4-trlazole.

SH C4He CH3 S-mereapto-4n-butyl-5-methyl-l, 2,4-triazole SH CH Z-furyl 3-rtmiarcaFto-4-methyl-6-(2-lury1) -1, 2, 4-

r azo e.

SH C 11 ..do 3-mercapt0-4-n-buty1-5-(2-furyl)-1, 2,

-trlazole.

SH Phenyl. "do 3-mercapto-4-phenyl-6-(Z-furyl) l, 2,

4-triazole.

SH CH COOH 3-mercapto-4-methyl-5-earboxy-1,2,4-trlazole.

SH 0 H; COOH 3-1531 apto-4-n-butyl-5-carboxy-l,2,

- nazo e.

SH C 11 C O OH. (HO CHZCHmN Triethanolamine salt of fi-mercaptot-n-butyl- 6-earboxy-1,2,4-triazole.

SH CrHn C OOC H 3-rirrreiarcarlato-4-n-butyl-5-earbethoxy-l,2,4-

azo e.

SNa C|H9 C O 0 0211 Sodium salt of 3-mereaptoi-butyl-fi earbethoxy-1,2,4-trlazole.

SC (0) NHCH: 0411 C 0 OH 3-methylcarbamoylmereapto-4-n-buty1-5- earboxy-1,2,4-triaz0le.

SC (0)NHCH 0411 00 OH. (HOCH2CH2)3N Triethanolamlne salt of 3-methylcarbamoy1- mercapto-4-n-buty1-5-earboxy-1,2,4-trlazole.

SC (S)N (CHM C4Ho COOH 3-dimethylthiocarbamoylmercapto-4-n-butyl- 6-carb0xy-1,2,4-trlazole.

-SCH 3-methylmercapto-4-n-butyl1,2,4-trlazole.

04H H Product from the cyanoethylation of Example 10 mmm Milli!!! 2-fieyanoethyl)-4-n-butyl-1,2,4-trlazoline-3- one. 3-(2-ethoxyethylmereapto)-4-n-butyl-1,2,4-

am e. 3-g2iphfinoxyethylmercapto)-4-n-buty1-1,2,4- r a o z e. 3-(1-hydroxy-2,2,2-trlchloroethylmercapto)-4- n-butyl-l,2,4-trlazo1e. 3-0arbamoylmethylmercapto-4-n-butyl-1,2,4-

trlazole. 3-( t-methoxybenzylmercapto)-4-n-butyl-1,2,4-

trlazole admixed with 4-n-butyl-2-(4-methoxybenzyl) -1,2,4-trlazoline-3-thione. 3-(2,4-dinitrophenylmercapto)-4-n-butyl-1,2,4-

trlazole. 8-methylcarbamoyhnercapto-4-n-butyl-1,2,4-

trlazole. 3-(2-bromobenzoylmereapto)-4-n-butyl-1,2,4-

trlazole.

TABLE I-Continued Example No.

R R R Name 45 CC|H4Br-4 C4H0 H 3-gl broinobenzoylmercapto)-4-n-butyl-1,2,4-

r1920 9. 46 SCOC6H1OCH6-4 04159 H 3-g lgfghoxypenzoyhnercapto)4-n-butylriazo e. 47 -SCOC6H4N0z-3 (34110 H 3-(t-riitrlobenzoylmercapto)-4-n-butyl-1,2,4-

. nazo e. 48 -SGOCH=CHCH=CHO Cilia H 3-Iuroy1mercapto-4-n-butyl-L2,4-triazole.

49 SCH2C0C0H4OCH9-4 CrHn H 3-(p l ng:oxyphenacyhnercapto)-4-n-butyl- 320 6. 60 Product from the cyanoethylatlon of Example 19 2-g2h-icyanoethyl) -4-p11enyl-1,2,4-triazoline-3- one. 51 SC6Ha(N02)a-2,4 3-(2,4-dlnitrof1henylmercapto)-4-pheny1- 1,2,4-triazo e. 62 SO0CH1OCH1-4 3-(4-methoxybenzoylmercapto)-4-pheny1- 1,2,4-trlazole. 53 SCOCH4NOz-3 3-(3-nitrobenzoyl)-4phenyl-1,2,4-trlaz0le.

TABLE 11.-CHARACTERIZATION 0F EXAMPLES Analysis or literature reference Example Melting point No. 0.) Empirical formula C H N S 1 120-125/.6 mm)"- C5H9Nz 52.8 (54.) 8.8 (8.1) 37.2 (37.9)

2 ISO-1421.2 mm. J. Chem. Soc. (C), 1967, 1665 3 145155/.05 mm- C9H15Nz 62. 6 (62. 7) 9. 8 (9. 8) 27. 2 (27. 5)

5- 37 CuHzgNz 68. 7 (68.9) 11. 1 (11. 0) 0.

. ClHuNxO 51. 5 (51. 0) 8. 3 (7. 8)

J Chem. Soc. (C), 1967,

Berichte 29, 2489 (1896) Berichte 29, 2487 (1896) C5HDN1S 42.2 41.9) 6.3 6. 3) 29.0 (29.4) 22.2 (22.3 r 11 46.0 (46.8) 7.1 7.0) 26.9 (26.8) 20.26 (20. 4 CoHuNaS 46.8 (46.8) 7.1 7.0) 26.9 (26.8) 20.2 20. 4 C1H1aN;S 49.0 (49. 1) 7.4 (7. 6) 24.3 (24.6) 18.9 (18.7) c1 IEN 61.8 (61.9 7.7 (8.1) 22.8 (22. 7) 17.4 (17.3) CroHmNzS 66.6 (66.4) 8.9 (8.9) 19.6 (19.7 16.2 (16. 0) CH19N3S 66.6 (66.4) 9.0 (8. 9) 20.0 (19. 7) 16.1 (16. 0 C12H23N6S 60.0 (69.7) 9.7 9. 6) 17.6 (17.4 13.3 13. 3 CaHmNaS 62.7 (62. 6 7.2 (7.1) 22.8 23.0) 17.8 17.6)

Saikoehi and Kanaoko Chem. Abstracts 56, 7305 Compt. rend. 248, 1677 (1959) C3H5N3OS 27 6 27.6) 4.0 3.8) 31.96 (32.1 24.6 24.4) CGH11N30S 41 9 (41.6) 6.46 6. 3) 24.4 (24.3) 18.4 (18.6) I Compt. rend 248, 1677 (1959) CTHliNa 48 9 (49. 1 7.8 (7. 6) 242 (24.6) 19.1 18.7) 0111119308 46 7 46.4) 3.9 3.9) 23.6 (23.2) 17.6 (17.7) C H NS 63.7 63.8) 6.8 (6.8) 18.9 (18.8 14.8 (14 4) C H N OS 69.2 (69.3) 3.96 (3. 7) 17.2 (17.3) 13.2 (13.1) CqH5N O4S 30.4 (30.2) 3.4 3.1) 26.7 (26. 4) 19.9 (20.1) C7H1IN3028 H20 38.1 (38.4) 6.9 (6. 9 19.1 (19.2) 14.7 (14.6) .C13H26N402S 61.8 (61.7) 8.8 (8.7) 18.8 (18.6 10.9 (10.6) CDHIGNgOzS 46 7 47.1) 6.7 6. 6) 18.6 18.3 144 (14.0

C0H14N40aS 41 8 40.9) 6.3 (6. 2 19.9 (19. 2) 11.4 (10.9) CIEHWNBOQS 0 (60. 6) 9.6 (8.1) 20.9 (19.6) 7.8 (8 9) 128-131/2 mink..- C7H13N3S 49.1 (49. 1 7.6 (7. 6) 246 (24.6) 19. 7) 168-176/2 1nmJ- C9H14N4S 61.2 61.4) 6.8 (6.7) 26.66 (26.7) 16.1 16.2 147-166/1mm.-- 01611618308 62.7 (62.3) 8.2 (8.3) 18.8 (18. 4) 14 46 14.0 220230/.25mm a H1IN3OS 60.9 (60.6) 7.3 (6. 9 16. 06 16.2) 10.9 11.6 96-97-- CaHnCIaNgOS 31.8 (31.6) 4.2 (3.96) 13.96 (13.8) 10.8 10. 6) 74-76.- O8H14N40 46.6 (44. 8) 6.3 6.6) 2 .7 (26.2) 14.3 (16.0) 190-206 01.11.919.08 60.6 (60. 6) 7.1 (6. 9) 1 .0 (16.2 10.96 (11.6) 106-107 0811 3185048 44.8 (44 6 4.3 (4. 0) 21.6 (21.7) 20.1 (19.8) 112-114.. O1H14N4OS 46.1 44.9) 6.7 (6. 6) 26,2 (26. 2) 14.8 (14.9 143-144-- 01111148116308 46.2 (46. 9 4.06 (46.1) 12.4 (12.3) 9.6 9.4 160-162-- C H BrN OS 46.8 (46.9 4.0 (4.1) 12.2 (12. 3) 9.6 (9.4) 94-96-.-- GuH N 67.7 (67. 7) 6.8 (6. 9) 14.4 (14.4) 11.0 (11.0 114-116-- C HHN 3S 61.0 (61. 0) 6.2 (4.6) 18.3 (18.3) 10.6 (10. 4

102-6-.-- CuI-IrgNaOzS 62.7 (62.6) 6.6 (6. 2) 16.0 (16.7) 12.7 (12.8

79-82-.-- C HrqNgO9S 68.1 (69.1 6.4 (6. 3 13.6 (13.8) 10.4 (10. 6

106-102.- Chemical Abstracts 63, 13242 (1966) 248-260.- C14H9N504S 49. (49.0 2.8 2. 6) 20.3 (20.4) 9.4 (9.3) 62.-- 174-176-- 01.11.318.028 61. (61.8 4.26 4.2) 13.6 (13.6) 10.6 (10.3) 63 143-146 C15H1N4Q1S 66 36 (66.2) 3.26 (3.1) 17.2 (17. 2) 9.9 (9.8

The number in parentheses represents the theoretical value as calculated from the empirical formula. Boiling point in 0.

Among the structures of this inventlon whlch are fungiby halogen, preferably chlorme, lower alkoxy, cyano, cidal the preferred compounds are those which are novel. hydroxy or nltro; aryloxy; alkoxy, alkyl, halo or mtro Novel structures wlthln this invention may be represented substituted aryloxy; aryl; alkoxy, alkyl, halo preferably by the structure chloro or nltro substituted aryl; benzoyl and halo pref/- erably chloro, alkoxy, alkyl or mtro substituted benzoyl, (c) the group --C(X)R wherein X is O or S and R l 1 18 selected from the group consisting of aryl, lower alkyl N SA substituted aryl, lower alkoxy substltuted aryl, halo and nitro substituted aryl, furoyl, and the NR R (X11) where n R and R may be hydrogen or lower alkyl wherein groups,

A is (d) the group -CH 'C(O)NR R wherein R and R have the above meaning,

(a) hydrogen, (6) the group CH(OH)R' whereinR" is hydrogen,

(b) lower alkyl groups and lower alkyl groups substituted lower alkyl or lower halo-substituted alkyl,

(f) the group wherein C and D are hydrogen and a meta-directing group such as cyano, nitro, sulfonic acid and sulfonic acid derivatives with the proviso that only one of C and D may be hydrogen,

(g) salt-forming metals such as the alkali and alkaline earth metals, cadmium, copper, iron, manganese, nickel and zinc;

When A is hydrogen R is alkyl of 3-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups; and cycloalkyl of 3-8 carbon atoms which may be substituted with one or more halo preferably chloro, hydroxy or nitro groups;

When A is methyl R is alkyl of 3-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups; aralkyl of up to 10 carbon atoms and aralkyl of up to 10 carbon atoms in which the aryl group is substituted with lower alkyl, halo preferably chloro and nitro groups;

When A is carbamoylmethyl, benzyl, nitrobenzyl or sodium R is alkyl of 1-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups; aralkyl of up to 10 carbon atoms and aralkyl of up to 10 carbon atoms in which the aryl group is substituted with lower alkyl, halo preferably chloro and nitro groups;

When A is all other values R is alkyl of 1-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups; cycloalkyl of 3-8 carbon atoms which may be substituted with one or more halo preferably chloro, hydroxy or nitro groups; aral-kyl of up to 10 carbon atoms; aralkyl of up to 10 carbon atoms substituted in the aryl group with lower alkyl, halo preferably chloro, and nitro groups; aryl; and lower alkyl, halo preferably chloro, and nitro substituted aryl; and

R is hydrogen, alkyl of 1-18 carbon atoms which may be substituted with one or more halo preferably chloro, lower alkoxy, hydroxy or nitro groups, furyl and the group -COOB wherein B is hydrogen, alkyl of 1-12 carbon atoms, ammonium, ammonium monosubstituted with lower alkyl or lower hydroxyalkyl, ammonium disubstituted with lower alkyl or lower hydroxyalkyl, amtmonium trisubstituted with lower alkyl or lower hydroxyalkyl, quaternary ammonium and salt-forming metals; and acid salts of the compounds of Formula XII which are basic.

Other novel structures within the scope of this invention and which are preferred fungicides may be depicted by the formula R (XIII) HOlN SH in wherein R is alkyl of 1-18 carbon atoms which may be substituted with one or more halo preferably chloro, alkoxy, hydroxy or nitro groups and cycloalkyl of 3-8 (XIV) carbon atoms which may be substituted with one or more halo preferably chloro, hydroxy or nitro groups.

Typical compounds within the scope of Formula XII, XIII and XIV include the following:

4-is0propyl-1,2,4-triazole 4-sec-butyl-1,2,4-triazole 4-n-pentyl-1,2,4-triazole 4-dodecyl-1,2,4-triazole 4-octadecyl-1,2,4-triazole 3-mercapto-4-isobutyl-1,2,4-triazole 3-mercapto-4 isopentyl-l,2,4-triazole 3-mercapto-4-undecyl-1,2,4-triazole 3-mercapto-4-(4-chlorobutyl)-1,2,4-triazole 3-mercapto-4-(4-methoxypropyl)-1,2,4-triazole 3-mercapto-4-(Z-hydroxybutyl) -1,2,4-triazole 3-mercapto-4-(4-nitrobutyl)-1,2,4-triazole 3-mercapto-4-cyclopropyl-1,2,4-triazole 3-methylmercapto-4- 3-chloropropyl -l ,2,4-triaz0le 3-ethylmercapto-4-butyl-1,2,4-triazole 3-butylmercapto-4-(2-ch1oropropyl)-1 ,2,4-triazole 3-chloromethylmercapto-4-butyl-1,2,4-triaz0le 3-(2-hydroxyethylmercapto)-4-butyl-1,2,4-triazo1e 3-(Z-cyanoethylmercapto)-4-butyl-1,2,4-triazole 3-(2-nitroethylmercapto)-4-butyl-1,2,4-triazole 3-[2-(4-chlorophenoxy) ethylmercapto1-4-butyl-1,2,

4-triazole 3- [2- (Z-methylphenoxy) ethylmercapto] -4-butyl- 1,2,

4-triazole 3- [2-(3-nitrophenoxy) ethylmercapto]-4-buty1-1,2,4-

triazole 3-benzylmercapto-4-butyl-1,2,4-triazole 3-(4-chlorobenzylmercapto)-4-butyl-1,2,4-triazole 3-(dodecylbenzylmercapto)-4-butyl-1,2,4-triazole 3-phenacy1mcrcapto-4-butyl-1,2,4-triazole 3- 3,5 -dichlorophenacy1mercapto -4-butyl- 1 ,2,4-triazole 3-benzoylmercapto-4-chloropropyl-1,2,4- triazole 3- 3-nitrob enzoylmercapto -4-b enzyl-l ,2,4-triazole 3-carbamoylmercapto-4-benzyl-1,2,4-triazole 3-methylcarbamoylmercapto-4- (4-chlorobenzyl -l ,2,

4-triazole 3-dimethylcarbamoylmercapto-4- 2-chloroethyl 1,2,

4-triazo1e 3-carbamoylmethylmercapto-4-(3-chloropropyl) -1,2,

4-triazole 3-carbamoylmethylmercapto-4-(Z-methoxybenzyl)-1,2,

4-triazole 3-carbamoylmethylmercapto-4- (4-nitrobenzyl)-1,2,

4-triazole 3-methylcarbamoylmethylmercapto-4-butyl-1,2,4-

triazole 3-hydroxymethylmercapto-4- (2-chlorobutyl)-1,2,4-

triazole 3-chloromethylmercapto-4-butyl-1,2,4-triazole 3- 1-hydroxy-2,4-dichloroethylmercapto) -4- 2-chloropropyl)-1,2,4-triazole 3-(2-nitrophenylmercapto-4- (3-bromopropyl) -1,2,4-

triazole 3- (2-cyanophenylmercapto) -4-butyl-1,2,4-triazole 3- (4-sulfonamidophenylmercapto) -4-benzyl-1,2,4-

triazole 3- 4-nitrophenylmercapto -4- (4-chlorobenzyl l ,2,4-

triazole 3-furoylmercapto-4- (3-chloropropyl)-1,2,4-triazole 3-furoylmercapto-4- (2-chlorobenzyl) -1,2,4-triazole 3-mercapto-4-(2-chloroethyl) -5-methyl-1,2,4-triazole 3-mercapto-4- (2-chlorobenzyl) -5-furyl-1,2,4-triazole 3-mercapto-4-(4-chlorobutyl)-5-buty1-1,2,4-triazole 3-mercapto-4- (2-bromopropyl) -5- 2-hydroxyethyl) 1,2,4-triazole 3-mercapto-4-benzyl-5-(2-nitroethyl)-1,2,4-triazole 3-mercapto-4-cyclopentyl-S-hydroxymethyl-1,2,4-

triazole 3-methylmercapto-4-butyl-5-methyl-1,2,4-triazole 3 -ethylmercapto-4- 3-chloropropyl) -5 -chloromethyl- 1,2,4-triazole 3- 2-chloroethylmercapto -4- Z-chloro ethyl) -5-carboxy-1,2,4-triazole 3-carbamoylmercapto-4- 3 -methoxypropyl) -5-carboxy-1,2,4-triazole 3- 3-methoxypropylmercapto -4- (4-chlorobenzyl -5- carboxy-1,2,4-triazole 3- (4-nitrophenylmercapto -4- 3 -bromopropyl -5 -carboxy-1,2,4-triazole 3-(4-methylbenzoylmercapto)-4-octyl-5-hydroxy-1,2,

4-triazole 3-mercapto-4-(2-hydroxyethyl)-5-hydroxy-1,2,4

triazole 3-mercapto-4- (2-chlorobutyl) -5-hydroxy-1,2,4-triazole The 1,2,4-triazoles of this invention and salts thereof possess biocidal properties and in this respect are particularly useful as agricultural fungicides. As such, they may be applied to various loci such as the seed, the soil or the foliage. For such purposes the 1,2,4-triazoles may be used in the technical or pure form as prepared, as solutions or as formulations. The compounds are usually taken up in a carrier or are formulated so as to render them suitable for subsequent dissemination as pesticides. For example, the 1,2,4-triazoles may be formulated as wettable powders, emulsifiable concentrates, dusts, granular formulations, aerosols, flowable emulsion concentrates. In such formulations, the compounds are extended with a liquid or solid carrier and, when desired, suitable surfactants are incorporated.

It is usually desirable, particularly in the case of foliar spray formulations, to include adjuvants, such as wetting agents, spreading agents, dispersing agents, stickers, adhesives and the like in accordance with agricultural practices. Such adjuvants commonly used in the art may be found in the John W. McCutcheon, Inc. publication Detergents and Emulsifiers 1967 Annual. Of course the surfactant should be selected relative to the specific triazole. In some instances the cationic 1,2,4-triazole salts may be incompatible with anionic surfactants and the anionic 1,2,4-triazole salts may be incompatible with cationic surfactants.

In case the 1,2,4-triazole compound is water-soluble, it may be dissolved directly in water to provide an aqueous solution for application. Similarly, the compounds of this invention may be dissolved in a water-miscible liquid, such as methanol, ethanol, isopropanol, acetone, dimethylformamide or dimethyl sulfoxide or mixtures of these with water and such solutions extended with water. The concentration of the solution may vary from 2% to 98% with a preferred range being 25% to 75%.

For the preparation of emulsifiable concentrates, the compound may be dissolved in organic solvents, such as xylene, pine oil, orthodichlorobenzene, methyl oleate, or a mixture of solvents, together with an emulsifying agent which permits dispersion of the pesticide in water. The concentration of the active ingredient in emulsion concentrates is usually to and in fiowable emulsion concentrates, this may be as high as 75 Wettable. powders suitable for spraying, may be prepared by admixing the compound with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents in such mixtures. The concentration of active ingredients in such formulations is usually in the range of 20% to 98%, preferably 40% to 75% Dusts are prepared by mixing the 1,2,4-triazoles with finely divided inert solids which may be organic or inorganic in nature. Materials useful for this purpose include botanical flours, silicas, silicates, carbonates and clays. One convenient method of preparing a dust is to dilute a wettable powder with a finely divided carrier. Dust concentrates containing 20% to 80% of the active ingredient are commonly made and are subsequently diluted to 1% to 10% use concentration.

The 1,2,4-triazoles can be applied as fungicidal sprays by methods commonly employed, such as conventional high-gallonage hydraulic sprays, low gallonage sprays, airblast spray, aerial sprays and dusts. The dilution and rate of application will depend upon the type of equipment employed, the method of application and diseases to be controlled, but the amount is usually 0.1 lb. to 25 lbs. per acre of the active ingredient.

As a seed protectant, the amount of toxicant coated on the seed is usually at a dosage rate of about 0.1 to 20 ounces per hundred pounds of seed. As a soil fungicide the chemical may be incorporated in the soil or applied to the surface usually at a rate of 0.1 to 25 lbs. per acre. As a foliar fungicide the toxicant is usually applied to growing plants at a rate of 0.25 to 10 pounds per acre.

The substituted 1,2,4-triazoles of this invention are also of interest when mixed with fertilizers and fertilizing materials. Such mixtures with fertilizers may be made in a variety of ways. For example, liquid formulations may be sprayed onto particles of mixed fertilizer or of fertilizer ingredients, such as ammonium sulfate, ammonium nitrate, ammonium phosphate, potassium chloride or sulfate, calcium phosphate or urea, singly or in admixture. Also, the toxicants and the solid fertilizing materials may be admixed in mixing or blending equipment. Similarly, a solution of toxicants in a volatile solvent may be applied to particles of fertilizer or fertilizer ingredients. A particularly useful form in which the toxicants are incorporated with fertilizers is in granular formulations. This type of solid composition serves a dual purpose in providing fertilizing material for the rapid growth of desired plants and at the same time helps control fungal diseases in one operation without the necessity of separate applications.

The compounds of this invention were evaluated as foliar fungicides for the control of wheat leaf rust, Puccinia recondila. In this test aqueous sprays were applied to about one week old wheat seedlings and the plants were allowed to dry. They were then inoculated with standard spore suspension of the Wheat leaf rust organism containing approximately 25,000 spores per ml. The plants were then held under standard conditions for the disease to develop. After about 7-9' days, lesions were counted and compared to those on untreated plants. The percent disease control was calculated. In a related test in order to determine the persistency of the sprays, the treated plants were rained upon for varying times in a standard rain machine in which six minutes of rain was equal to about one inch of rain. Table III gives the results.

TABLE III Wheat leaf rust control by foliar application Percent control Without rain With rain Example No. 11b. 0.25 lb. 1 lb. 0.25 lb Percent control 18 n-butyl-1,2,4-triazole and 3-mercapto-4n-butyl-S-carboxy- 1,2,4-triazole.

As one test for systemic activity the compounds were Withoutraifl with rain evaluated by a root-uptake method. In the root-uptake Example No. 11b, 0,2511% test one of the active compounds of this invention, con- 100 mo 83 82 tamed m a suitable formulation, was incorporated into 99 93 100 100 the S011 by elther spraying it into a rotating drum of soil, 18g 32 188 $3 or by drenching the soil. The dosage of active ingredient 99 99 100 1 0 in the S011 ranged from about 50.0 to about 2.5 parts per $8 18g %8g $8 10 million (p.p.m.). Seeds of a susceptible wheat variety r 8 1 5 were planted in the treated soil and allowed to germinate m0 100 100 100 and grow to a height of about 4 inches. The plants were igg igg lg? 8% then moculated wlth a spore suspension of Pucciniw re- 100 100 100 93 condita. The plants sprayed with spores of the rust fungus 13g 18g 3g 15 were then held at 70 F. in a moist chamber about 16 188 igg $8 igg hours to permit the development of infection. The 100 100 100 100 lesions were allowed to develop about one week and 3 3g %88 188 were then counted in comparison to untreated plants and 100 100 100 100 20 the percent disease control calculated. Similar tests 33 33 38 32 were conducted using the wheat stem rust organism i 3 99 100 Puccinia graminis instead of Puccinia recondita. Table IV gives the results.

TABLE IV.SYSTEMIC ACTIVITY BY ROOT-UPTAKE Percent systemic wheat leaf rust control ppm. in soil Example o. R R R" 10 5 2.5

1 H C3H1 H 100 99 2. H -04H, H 100 100 100 3-- H CcHrz H 92 77 5 H -CH2CH2CH2OCH3 H 99 96 6.. H CH2C.H5 H 99 98 96 9 sH 03111 H s4 s2 40 10- SH 04m H 100 97 83 12- SH 05H H 97 97 97 13.-.. SH CaHrs H 54 0 0 1s- -SH CHrClHa H 64 34 0 28- -sH 04H 00011 100 99 95 29- -SH C4H9 COONH (CHzCHzOH); 100 99 98 30.. -SH C4119 COOCzHs 100 95 93 a1. -SNa 04119 0000211; 99 97 85 32. so O)NHCHa 04H 000B 100 99 96 33- -SC(O)NHOH3 04H COONH(OH2CH2OH)| 99 99 89 34- SC(S)N(CH,) 04H COOH 100 96 88 36 (2-(2-eyanoethyl) -4-n-butyl-1, 2, t-triazoline-a-thione) 92 86 82 37- SCH2CH90C2H5 C4H9 H 89 85 52 a9. -SCH(OH)CC11 04H H 100 100 98 40. SCH:C(O)NH2 olHq H 92 91 7e 41 -SCH2CaH40OH -4 6411. H 72 71 64 42- -SCtH (N 0) 2-2, 4 04H: H 100 94 67 43... -so( HCHz 0411 H 100 100 96 49""- -so(o)o.H.ooH,-4 04H. H 100 100 99 4s. S-iuroyl 0411 H 99 99 94 49. SCHzOOCnH40OH9-4 C4H9 H 44 68 Other tests in which the spray was allowed to age for several days before being rained upon demonstrated excellent persistency.

The compounds of this invention which have exhibited excellent systemic activity in the control of cereal rusts are of the structure wherein R is hydrogen or the group --SA wherein A is hydrogen, cyano-substituted lower alkyl, lower alkoxy substituted lower alkyl, the group CH(OH) CCl --CH NR -R wherein R and R are hydrogen or lower alkyl, benzyl, methoxybenzyl, the group C(X)NR R wherein X is O or S and R and R are hydrogen or lower alkyl, methoxy benzoyl, furoyl, 2,4-dinitrophenyl and saltforming metals; R is alkyl of 3 to 6 carbon atoms exclusive of the tert-butyl group, lower alkoxy lower alkyl and 'benzyl; and R" is hydrogen or the -COOB group wherein B is hydrogen, lower alkyl or a metal, ammonium, amine or quaternary ammonium salt-forming group.

The preferred compounds are those in which R" is an n-butyl group, e.g. 4-n-butyl-1,2,4-triazole, 3-mercapto-4- Another type of evaluation as a systemic fungicide was by seed treatment. In this test wheat seeds were treated with varying dosages of the test compound :by mixing 3 cc. of an acetone: methanol -(1:1) mixture containing the test compound with 50 grams of seed. The treated seeds were dried and stored for 24 hours. The seeds were planted and nine days after planting were inoculated with a standard spore suspension of wheat stem rust, Puccinia graminis. Lesions were allowed to develop and 9 days after inoculation were counted in comparison with plants produced from untreated seed and the percent disease control calculated. The following Table V gives the results using three rates of application at 0.5 ounce, 1 ounce and 3 ounces of the test compound per 100 lbs. of wheat seed.

In other seed treatment tests almost complete control of wheat leaf rust was obtained with the compounds of this invention thirty days or more after seed treatment.

Another type of systemic test was run in which pots of approximately 5 inch high wheat plants were sprayed with varying concentrations of the test compound. Thirtysix hours later they were sprayed six minutes in a rain machine which amounted to about one inch of normal rainfall. The plants were then placed in a greenhouse for 7 days and then inoculated with a spore suspension of wheat leaf rust, Puccinia recondita. About 7 days later lesion counts were made on ten leaves representing the sprayed leaves and new growth from each replicate and compared with similar pots of wheat plants which were untreated with a chemical and the percent disease control determined. Disease control on the new growth is a measure of systemic activity. The commercial product known by the trademarked name Plantvax, which is 2,3- dihydro 5 carboxanilido 6 methyl 1,4 oxathiin- 4,4-dioxide, was used as a standard. Table VI gives the results.

TABLE VI Foiiar systemic activity Percent rust control Sprayed leaf New growth (lb./10O gal.) (lb./l gal.) Treatment, Example No. Va M2 l6 $6 34 99 99 97 100 98 85 99 76 42 87 54 46 97 88 80 90 77 75 98 96 91 92 79 57 96 88 86 65 48 38 78 63 54 54 34 36 99 91 71 86 73 61 90 78 46 90 75 63 86 73 81 54 75 67 69 74 81 82 69 56 79 79 57 79 63 54 73 27 25 61 23 17 88 51 49 88 59 38 98 93 81 81 69 57 96 83 68 98 79 67 95 81 91 92 79 77 50 13 0 0 42 27 0 Plantvax 49 37 3 38 32 A field test was conducted in which 3-mercapto-4-nbutyl 1,2,4 triazole (the compound of Example Plantvax and maneb (manganese ethylenebisdithiocarbamate) were evaluated for the control of leaf. rust on winter wheat planted in September. Applications of the chemicals were made the following April when the wheat was 16-24 inches tall and in the boot stage. The volume of spray was 40 gallons per acre. Forty-six days after application lesion counts were made of 200 leaves per plot for four replications and compared with check (untreated) plots. This gives a measure of systemic control. Table VII gives the results.

TABLE VII Systemic Field Test No. of lesions] A field test was conducted in which the compound of Example 10, the compound of Example 28, and Plantvax were evaluated for the control of leaf rust on spring wheat planted on May first. Forty one days after planting spray applications of the chemicals were made in a dosage series. Thirty-six days after treatment the disease control was evaluated by determining the percent leaves infected. Table VIII gives the results.

Representative compounds of this invention have given good control of various fungal organisms. For example, compounds of the type I (XVI) wherein R is lower alkyl, R is hydrogen and carboxy and its triethanol amine salts, R and R are hydrogen or lower alkyl, and X is 0 or S have given or better kills of Phytophthora infestans at 1200 p.p.m. The compound 3 (4 methoxybenzylmercapto)-4-butyl 1,2,4-triazole gave 50-85% control of Botrytis cinerea on broad bean at 1200 p.p.m. When'beets were grown in a soil containing 200 p.p.m. of 3-(4-methoxybenzoylmercapto)- 4-butyl-1,2,4-triazole, an excellent control of Pythium ultimum was obtained.

The compounds of this invention may be utiliied as the sole biocidal agents, alone or in admixture, or they may be employedin conjunction with other fungicides or with insecticides, miticides, bird repellents and comparable pesticides.

Fungicides which may be combined with the 1,2,4-triazoles of this invention include dithiocarbamates and derivatives such as ferric dimethyldithiocarbamates (ferbam), zinc dimethyldithiocarbamate (ziram), manganese ethylenebisdithiocarbamate (maneb) and its coordination product with zinc ion, zinc ethylenebisdithiocarbamate (zineb), tetramethylthiuram disulfide (thiram) and 3,5- dimethyl l,3,5-2H-tetrahydrothiadiazine-Z-thione; nitrophenol derivatives such as dinitro-(1-methylheptyl)phenyl crotonate (dinocap), 2-sec-butyl-4,6-dinitrophenyl 3,3-dimethylacrylate (binapacryl) and 2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate; heterocyclic structures such as N-trichloromethylthiotetrahydro-phthalimide (captan), N-trichloromoethylthiophthalimide (folpet), 2-heptadecyl-Z-imidazoline (glyodin), 2,4-dichloro-6-(o-chloroanilino)-s-triazine, diethyl phthalimidophosphorothioate, 5 -amino-1 [bis dimethylamino phosphinyl] -3 -phenyl- 1,2,4-triazole, 5-ethoxy-3-trichlorornethyl-1,2,4-thiadiazole, 2,3-dicyano-1 ,4-dithiaanthraquinone (dithianon) 2-thio-1,3-dithio- [4,5 -b] quinoxaline (thioquinox) l-(butylcarbamoyl)-2-benzimidazole carbamic acid methyl ester,

4-(2-chlorophenylhydrazono)+3-methyl-5-isoxazolone,

pyridine-Z-thiol-l-oxide,

8-hydroxyquinoline,

2,3-dihydro--carboxanilido-6-methyl-1,4-oxathiin- 4,4-dioxide, and

bis (p-chlorophenyl)-3-pyridinemethanol;

and miscellaneous fungicides such as dodecylguanidine acetate (dodine), 3-[2-(3,5-dimethy1-2-oxycyclohexyl)-2- hydroxyethylJglutarimide (cycloheximide), phenylmercuric acetate, N-ethylmercuri-1,2,3,6-tetrahydro-3,6-endomethano 3,4,5,6,7,7-hexachlorophthalimide, phenylmercuric monoethanolammonium lactate, 2,3-dichloro-1,4-

naphthoquinone, 1,4-dichloro2,5-dimethoxybenzene, pdimethylaminobenzenediazo sodium sulfonate, 2-chlorol-nitropropane, polychloronitrobenzenes such as pentachlorom'trobenzene, methyl isothiocyanate, fungicidal antibiotics such as griseofulvin or kasugamycin, tetralfluoro'dichloroacetone, 1-phenylthiosemicarbazide, Bordeaux mixture, nickel-containing compounds and sulfur.

Herbicidal or plant growth regulatory activity has been observed with certain of the 4-substituted-1,2,4-triazoles of this invention (Formula I) which have the formula below:

R" (XVII) wherein R is alkyl, straight or branched, of 1 to 18 carbon atoms, which may be substituted with a lower alkoxy or a hydroxy group; aralkyl from 7 up to carbon atoms; which may be substituted in the aryl group with one or more halo, preferably chloro, groups; aryl, preferably phenyl; or halo, preferably chloro, substituted aryl.

Examples of these structures are given in Table IX.

TABLE IX TABLE X Phytotoxicity of 4-substltuted-l, 2, 4-triazoles, average percent iniury A field test was conducted using 4-butyl-1,2,4-triazole (Example 2) as the test compound. This was applied to a wheat (Pennoll variety) field in which the wheat was approximately six inches tall and tillering, and a natural population of weeds about two inches tall was present. Dosage rates of 0.5, 1 and 2 pounds per acre (0.55, 1.1 and 2.2 kilograms per hectare) were applied as an aqueous spray in a carrier volume of gallons per acre. Ten days after treatment, the extent of weed control was observed. There was slight inhibition of the weeds at 0.5 pound per acre, and at 1 pound per acre there was moderate to severe inhibition. At 2 pounds per acre, there was severe inhibition, particularly of pigweed (Amaranthus spp.) and purslane (Portulaca oleracea). It was'estimated that these weeds are controlled to the extent of greater than 90%.

For herbicidal and plant growth regulation purposes, the compounds of Formula XVII are applied in a plant growth regulating amount, which generally is in the range of 0.5 to 20 pounds per acre and preferably at 1 to 5 pounds per acre.

4-Substltutcd-1,2,4-triazoles oi. the formula Melting C.) or Analytical data, percent boiling point Empirical C./mm.) formula 0 H N 128132I.1mm ClHllNl 57.8 (57.6) 9.2 (8.8) 33.6 (33.6) 153-163I.2 mm.'- CTHHN: 60.5 (60.4) 9.7 (9.4) 30.4 (30. 2) 147/. 05111111.. CioHnNs 66.0 (66.3) 10.8 (10.6) 23.4 (23.2) 167-174/.01mm cmHmN, 65.7 (66.3) 10.7 (10.6) 24.4 (23.2) 51-5 CuHrrN; 70.5 (70.9) 10.6 (11.5) 17.5 (17.7) semisolid 0.1191940 46.8 (47.2) 7.6 (7.1) 29.9 (33.0) 145-149/.05 C|H1 N 0 49.5 (51.0) 7.3 (7.9) 29.8 (29.8) 125-132/2 C7HnNx0 53.2 (54. 2) 8.7 (8.4) 27.6 (27.1) 156-164/.2mm ClHflNaO 59.6 (56.8) 8.3 (8.9) 25.5 (24.8) 118-12 ClH1N| J. Chem Soc. 1967, 1664 203-206 CsH ChN J. Med. Pharm. Chem. 5, 383 (1952) 172-174" CQHsChN; 45.1 (44 9) 2.3 (2.3) 19.4 (19.6 200-208/.05mm- CaH ClN; 55.7 (55.8) 4.6 (4.1) 21.7 (21. 7 169-171 o.H1Cl5N| 47.7 (47.5) 3.4 (3.1) 18.4 (18.4) 133-135 C0H1ClzNg 47.6 (47.5) 3.2 (3.1) 18.5 (18.4)

* Figures in parentheses are those calculated from the empirical formula.

In evaluatmg compounds for phytotoxicrty, a standard We clalm: test, known as a prelrmlnary postemergence herbrcrdal 1. Acompound of the formula: evaluation, was used. For this test, the compounds were applied at a rate of 10 pounds per acre (11 kilos per hectare) using an aqueous spray at a carrier rate of about gallons per acre. Typical monocotyledonous (monocots) and typical dicotyledonous (dicots) plants were sprayed with the test chemical two weeks after planting, and the average percent injury was observed two weeks later. Results obtained are given in Table X.

wherein R is alkyl of 3-18 carbon atoms.

2. A compound as defined in claim 1 wherein R is alkyl of 3-6 carbon atoms.

24 OTHER REFERENCES 2 3. A compound as defined in claim 1 wherein R is a Beilsteins Handbuch der Organischen Chemie, vol. 26, (Vierte Auflage, Berlin, 1937), pp. 142-143. Potts, Chemibutyl group.

4. A compound as defined in claim 1 which is 3-rner- 5 cal Reviews, vol. 61, pp. 98-99 (1961).

capto-4-n-butyl-1,2,4-triazo1e.

References Cited UNITED STATES PATENTS ALTON D. ROLLINS, Primary Examiner 3,594,390 7/1971 Timmler et a1. 260-308 CL FOREIGN PATENTS 10 71-92; 260-308 c, 347.2, 481 R; 424269 1,423,516 11/1965 France 260308 1,549,674 11/1968 France 260--308 

